Estrogen receptor related alpha (ERRalpha) is an orphan nuclear receptor
that is closely related to the estrogen receptor. It is expressed in a
variety of adult and embryonic tissues (in particular, at the onset of
ossification), as well as in several osteoblastic cell lines. ERRalpha acts
as a site-specific, cell-specific transcriptional activator. Here, we show
that ERRalpha transactivates the promoter of the mouse osteopontin (OPN)
gene, the product of which is a marker of the late stages of osteoblastic
differentiation. This effect is cell specific and is exerted through
derivatives of the ERRalpha response element. Overexpression of ERRalpha in
three different osteoblast-like cell lines results in an elevation of the
amount of OPN-corresponding mRNA. Therefore, OPN is a target gene for
ERRalpha, pointing to the role of the latter in osteoblast differentiation.